Age-standardized incidence, prevalence, and mortality rates of autoimmune diseases in adolescents and young adults (15–39 years): an analysis based on the global burden of disease study 2021

Background Autoimmune diseases (ADs) present significant health challenges globally, especially among adolescents and young adults (AYAs) due to their unique developmental stages. Comprehensive analyses of their burden are limited. This study leverages the Global Burden of Disease (GBD) 2021 data to assess the global, regional, and national burden and trends of major ADs among AYAs from 1990 to 2021. Methods Utilizing data from the Global Burden of Disease (GBD) Study 2021 for individuals aged 15–39 years, we employed a direct method for age standardization to calculate estimates along with 95% uncertainty intervals (UIs) for assessing the age-standardized incidence rates (ASIR), prevalence rates (ASPR), and mortality rates (ASMR) of ADs. The diseases analyzed included rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), Asthma, and Psoriasis. Trends from 1990 to 2021 were analyzed using Joinpoint regression, providing average annual percentage changes (AAPC) and 95% confidence intervals (CIs). Result In 2021, the global ASIR, ASPR, and ASMR of RA among AYAs (per 100,000 population) were 9.46 (95% UI: 5.92 to 13.54), 104.35 (77.44 to 137.84), and 0.016 (0.013 to 0.019), respectively. For IBD, the corresponding rates were 4.08 (3.07 to 5.37), 29.55 (23.00 to 37.83), and 0.10 (0.07 to 0.12). MS exhibited rates of 1.40 (0.93 to 1.93), 16.05 (12.73 to 19.75), and 0.05 (0.04 to 0.05), respectively. T1DM had rates of 6.63 (3.08 to 11.84), 245.51 (194.21 to 307.56), and 0.54 (0.47 to 0.60). Asthma demonstrated rates of 232.22 (132.11 to 361.24), 2245.51 (1671.05 to 2917.57), and 0.89 (0.77 to 1.08). Psoriasis showed rates of 55.08 (48.53 to 61.93) and 426.16 (394.12 to 460.18) for ASIR and ASPR, respectively. From 1990 to 2021, the global ASIR of RA (AAPC = 0.47, 95% CI: 0.46 to 0.49), IBD (0.22 [0.12 to 0.33]), MS (0.22 [0.19 to 0.26]), T1DM (0.83 [0.80 to 0.86]), and Psoriasis (0.33 [0.31 to 0.34]) showed increasing trends, whereas Asthma (-0.96 [-1.03 to -0.88]) showed a decreasing trend. The global ASPR of RA (0.70 [0.68 to 0.73]), MS (0.35 [0.32 to 0.37]), T1DM (0.68 [0.66 to 0.69]), and Psoriasis (0.29 [0.27 to 0.32]) also showed increasing trends, whereas IBD (-0.20 [-0.27 to -0.13]) and Asthma (-1.25 [-1.31 to -1.19]) showed decreasing trends. Notably, the estimated global ASMR of RA (-2.35 [-2.57 to -2.12]), MS (-0.63 [-0.86 to -0.41]), T1DM (-0.35 [-0.56 to -0.14]), and Asthma (-1.35 [-1.44 to -1.26]) in AYAs declined. Additionally, the burden of disease for ADs in AYAs varies considerably across continents and between 204 countries and territories. Conclusion ADs among AYAs present a substantial public health burden with notable regional disparities in incidence, prevalence, and mortality rates. Understanding these patterns is essential for developing targeted public health interventions and policies to mitigate the impact of ADs in this population. Supplementary Information The online version contains supplementary material available at 10.1186/s12889-024-19290-3.


Introduction
Autoimmune diseases (ADs) are characterized by chronic inflammatory responses resulting from immune dysregulation and loss of self-tolerance.This often leads to chronic tissue and organ damage, affecting approximately 7.6-9.4% of the global population [1].Adolescents and young adults (AYAs), ranging from approximately 15-39 years of age, represent a population undergoing significant physical, emotional, and psychosocial changes [2][3][4].Studies have indicated that ADs can pose serious health risks to AYAs [5][6][7].However, previous epidemiologic studies on ADs have primarily focused on entire populations or elderly populations [8][9][10], with few reported in AYAs.
AYAs constitute a unique demographic likely to experience heightened physical or psychological stress compared to other age groups.This is attributed to the simultaneous occurrence of specific events in this age group, such as marriage, initiation of full-time employment, and living independently away from their parents.These factors may contribute to unhealthy conditions, making them less adherent to the treatment of their illnesses and increasing the risk of poor self-management [11].ADs not only challenge the health of AYAs during the initial stages of the disease but also pose significant risks for long-term health consequences that can profoundly impact their lives.Rheumatoid arthritis (RA) in AYAs often leads to a lifetime burden of chronic pain and joint deformity, escalating the risk of early-onset osteoporosis and cardiovascular diseases [12].Similarly, inflammatory bowel disease (IBD) can severely disrupt nutrient absorption, leading to growth impairments and increased susceptibility to colorectal cancer later in life [13].Multiple sclerosis (MS), diagnosed in young adults, frequently results in progressive neurological decline, significantly reducing life expectancy and quality of life [14].Adolescents with type 1 diabetes mellitus (T1DM) face lifelong challenges, including the risk of diabetic nephropathy and cardiovascular complications, which are major causes of morbidity and mortality in this group [15].Asthma in AYAs can lead to chronic respiratory dysfunction, impacting physical activity and increasing the likelihood of chronic obstructive pulmonary disease in later years [16].Psoriasis, often perceived as a skinonly disease, has systemic manifestations that include an increased risk of metabolic syndrome and cardiovascular disorders, further complicating the health landscape for affected AYAs [17].Therefore, ADs in AYAs emerge as a significant public health issue.There is an urgent need for a comprehensive analysis and characterization of the incidence, prevalence, and mortality rates, along with their trends in recent years, in young populations worldwide.Such insights are critical for policymakers in developing primary prevention strategies.
In this study, we utilized the GBD 2021 dataset to extract global, regional (African Region, Eastern Mediterranean Region, European Region, Region of the Americas, South-East Asia Region, Western Pacific Region), and national (204 countries or territory) data about ADs (RA, IBD, MS, T1DM, Asthma, and Psoriasis) in the AYAs.Subsequently, we standardized and estimated the age-standardized incidence, prevalence, and mortality rates.Furthermore, we conducted a comprehensive analysis of the trends in these three rates over the last 30 years, aiming to provide valuable insights for the global prevention and control of ADs.

Data source
The Global Burden of Disease Study (GBD) is the largest and most comprehensive global observational epidemiologic survey to date.It offers a thorough assessment of health losses across 204 countries and territories, encompassing 369 diseases and injuries, as well as 88 risk factors, spanning the years 1990 to 2021 18, 19 .
A detailed description of the original data and methodology of GBD has been described in previous publications [18][19][20][21].In brief, the burden of disease was estimated using a wide range of data from a representative population.These data were derived from literature reviews and identified through research collaborations, which included published scientific reports of registries and cohorts, data from cohort and registry studies, administrative health data and reports, and population surveys.DisMod-MR 2.1, an epidemiologic state-transition disease modeling software, together with MR-BRT, a Bayesian meta-regression software, were used to produce consistent disease estimates.Uncertainty intervals (UIs) were calculated from 1000 draw-levels from the posterior distribution of models, and 95% UIs were defined as the 2.5th and 97.5th values of the distribution [20,22].

Statistical analysis
The age-standardized rates (ASRs) estimates were calculated using the direct method of standardization and were weighted using the GBD 2021 world standard population [18,23].The ASRs were reported per 100,000 population with corresponding 95% UI.To further analyze the trends in age-specific autoimmune disease incidence, prevalence, and mortality rates at the global, continental, and national levels, this study employed Joinpoint regression analysis [24].
Joinpoint regression software (version 5.1.0,available at https://surveillance.cancer.gov/joinpoint/) was used to analyze trends.Joinpoint analysis facilitates the assessment of trends (1990-2021) by calculating the average annual percentage (%) change (AAPC) and its 95% confidence interval (CI).Trends were categorized as upward (AAPC > 0), downward (AAPC < 0), or stable (95% CI including 0).It is worth noting that UIs differ from CIs in that CIs can only capture uncertainty associated with sampling error, whereas UIs provide a method for propagating uncertainty from multiple sources such as sampling, model estimation, and model specification [22].
To assess the variation in ASIR, ASPR, and ASMR of major ADs across different regions and countries in 2021, we calculated the extremal quotient and coefficient of variation.
Extremal Quotient (EQ) measures the range and disparity of data between different continents and countries.The formula is as follows [25]: Coefficient of Variation (CV) measures the relative variability of the data.The formula is as follows [26]: By calculating the ratio of the standard deviation to the mean for each disease and each metric, we can assess the relative variability of the data across different continents and countries.Data collation and visualizations were conducted using R software (Version 4.3.1).A threshold of 0.05 for the two-tailed P-value was employed to establish statistical significance.

Variation across countries
In 2021, the comparison of major ADs across different countries reveals significant differences in ASIR, ASPR, and ASMR.For ASIR, the greatest difference is observed in IBD, with an EQ of 166.074 and a CV of 1.259, while the smallest difference is seen in asthma, with an EQ of 8.057 and a CV of 0.398.For ASPR, the greatest difference is also in IBD, with an EQ of 157.823 and a CV of 1.300, and the smallest difference in psoriasis, with an EQ of 13.835 and a CV of 0.572.For ASMR, the greatest difference is observed in RA, with an EQ of 179600.9 and a CV of 1.362, while the smallest difference is in T1DM,  S11)

Data supplementation
We provide "Burden of AD in adolescents (15-24 years, as defined by the World Health Organization [27,28])" in the Supplementary Material (Table S12-16), which the reader is invited to review.

Discussion
This study is the first to comprehensively analyze the burden of six major ADs-RA, IBD, MS, T1DM, Asthma, and Psoriasis-among AYAs in recent years.Utilizing data from the GBD 2021, we conducted a detailed examination of the ASIR, ASPR, and ASMR of these diseases globally and across various regions and countries.Additionally, we explored the trends in these rates from 1990 to 2021.

Rheumatoid arthritis
RA shows an increasing trend in both ASIR and ASPR among AYAs, with a notable decline in ASMR.This indicates a growing chronic burden on this age group.Improved diagnostic capabilities and changes in environmental risk factors likely contribute to this trend.The impact of RA on quality of life and productivity due to chronic pain and joint deformity underscores the need for early diagnosis and long-term management strategies [29,30].This trend aligns with previous studies that have reported similar increases in RA incidence and prevalence among younger populations due to improved diagnostic capabilities and changing environmental risk factors [31,32].

Inflammatory bowel disease
IBD exhibits significant downward trends in both ASIR and ASPR globally, while the ASMR remains stable.The European Region has the highest rates, possibly due to genetic predispositions and environmental factors [33,34].In contrast, the lowest rates are observed in the African Region.The disruption caused by IBD in terms of appetite, weight loss, and fatigue highlights the necessity for early and effective interventions.This finding is consistent with studies that have shown higher IBD prevalence in Europe and North America compared to Africa and Asia [34].

Multiple sclerosis
MS shows an upward trend in both ASIR and ASPR globally, with a decline in ASMR.The European Region has the highest incidence, prevalence, and mortality rates.MS diagnosed in AYAs often results in progressive neurological decline, significantly reducing life expectancy and quality of life [35,36].Continuous support and rehabilitation services are crucial to address these long-term health needs.According to Kingwell et al., MS is the most common cause of neurological disability in young adults worldwide and approximately half of those affected are in Europe [37].Continuous support and rehabilitation services are essential to address the long-term health needs of AYAs with MS.

Type 1 diabetes mellitus
T1DM presents the highest ASIR and ASPR among the ADs studied, with a significant upward trend globally.The European Region has the highest rates, while the Western Pacific Region has the lowest.T1DM poses lifelong challenges, including the risk of diabetic nephropathy and cardiovascular complications [38,39].Strengthening primary prevention and early intervention strategies is essential to manage this rising incidence and its long-term impacts.These results are in line with studies that highlight the high incidence of T1DM in Nordic countries and other parts of Europe [40], attributed to genetic factors and possibly environmental triggers [41].

Asthma
Asthma demonstrates significant decreases in ASIR, ASPR, and ASMR globally, indicating effective public health interventions and management strategies [16].The Region of the Americas shows the highest incidence and prevalence, while the African Region has the highest mortality.Continuous vigilance is necessary to sustain these gains and address emerging challenges.This trend of decreasing asthma incidence and prevalence has been documented in other studies, suggesting improvements in asthma management and public health policies globally [42].

Psoriasis
Psoriasis shows consistent increases in both ASIR and ASPR globally, with significant regional differences.The highest rates are observed in Europe, indicating a higher burden of this disease.The chronic nature of psoriasis and its impact on physical and psychological health necessitate comprehensive care approaches to improve the quality of life for affected individuals [43,44].Previous literature corroborates these findings, showing that psoriasis prevalence is highest in Europe and North America, likely due to genetic factors and possibly lifestyle influences [42].Addressing the psychosocial aspects and providing holistic management strategies are essential for improving the quality of life for affected individuals.

Regional and national variations
This study highlights significant regional and national variations in the burden of ADs among AYAs.Highincome regions, such as the European Region and the Region of the Americas, generally exhibited higher ASIR and ASPR.These higher rates can be attributed to better diagnostic capabilities and more advanced healthcare infrastructure [45].However, these regions also showed lower ASMR, reflecting effective disease management and treatment protocols.In contrast, low-and middleincome regions, such as the African Region and the South-East Asia Region, often demonstrated lower ASIR and ASPR but higher ASMR, indicating potential gaps in healthcare access and quality.These disparities emphasize the need for tailored public health strategies and international collaboration to address the unique healthcare challenges and improve outcomes for AYAs in different regions.

Variation of ASRs across regions and countries
Regionally, MS demonstrated the greatest difference in ASIR.This significant variability can be influenced by genetic predispositions and environmental factors such as latitude, particularly in Europe and North America, where healthcare systems are more advanced [46,47].On the other hand, RA exhibited the smallest difference in ASIR, indicating a more uniform global distribution of risk factors but still higher rates in high-income regions due to superior healthcare infrastructure and diagnostic capabilities [48].
Nationally, countries with well-developed healthcare systems, especially in Europe and North America, report higher ASIR and ASPR, reflecting better diagnostic and treatment facilities [49,50].Conversely, lower-income countries often show lower ASIR and ASPR but higher ASMR, highlighting disparities in healthcare access and quality [51].These disparities underscore the need for tailored public health strategies and international collaboration to address these differences and improve outcomes for individuals with autoimmune diseases in different regions and countries.

Limitations
Several limitations of this study should be noted.First, the GBD data relies heavily on modeling, which may introduce biases due to the variable quality of primary data from different countries.These biases can lead to inaccuracies in estimating the true burden of ADs.For instance, underreporting in low-income regions or overestimation in areas with better diagnostic facilities could skew the results.Second, the analysis did not include subgroup analyses, which could provide more detailed insights into the burden of ADs in specific populations.Subgroup analyses by gender, socioeconomic status, or specific age brackets within the AYA group could reveal more nuanced patterns and risk factors, aiding in the development of targeted interventions.Third, the variability in healthcare infrastructure and data collection methods across different regions and countries may affect the comparability of the results.Disparities in health system performance, disease surveillance, and reporting standards can introduce inconsistencies in the data, potentially leading to misinterpretations.

Conclusion
ADs in AYAs present a significant public health challenge, with considerable variability in incidence, prevalence, and mortality rates across regions and countries.Understanding these patterns is crucial for developing targeted public health interventions and policies.This study provides valuable insights into the epidemiological landscape of ADs in AYAs, laying the groundwork for future research and improved healthcare strategies.Effective management of ADs in AYAs requires a comprehensive approach that includes early diagnosis, effective treatment, and ongoing support to improve long-term health outcomes.

Fig. 3 Fig. 6
Fig. 3 ASIR, ASPR and ASMR of IBD in AYAs at the national level in 2021 (A, B, C), and their changing trends from 1990 to 2021 (D, E, F)

Fig. 5
Fig. 5 ASIR, ASPR and ASMR of MS in AYAs at the national level in 2021 (A, B, C), and their changing trends from 1990 to 2021 (D, E, F)

Fig. 7 Fig. 9
Fig. 7 ASIR, ASPR and ASMR of T1DM in AYAs at the national level in 2021 (A, B, C), and their changing trends from 1990 to 2021 (D, E, F)

Table 1
ASIR, ASPR and ASMR of autoimmune diseases in adolescents and young adults at the global and regional levels in

Table 2
to 1.25]), while Region of the Americas (-0.05 [-0.09 to -0.02]) decreased the most.The region with the largest increase in ASMR was the South-East Asia Region (2.35 [2.01 to 2.68]), while the largest decrease occurred in European Region (-1.77[-2.21